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胰岛素样生长因子Ⅱ基因印迹丢失在结直肠腺瘤中的意义

Loss of Imprinting of Insulin-like Growth Factor Ⅱ and its Significance in Colorectal Adenoma

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【作者】 蔡军; 张亚历; 付祥胜; 周永柏;

【Author】 CAI Jun;ZHANG Yali;FU Xiangsheng;ZHOU Yongbai;Department of Gastroenterology,Nanfang Hospital,Southern Medical University;

【通讯作者】 张亚历;

【机构】 南方医科大学南方医院消化内科;

【摘要】 背景:胰岛素样生长因子Ⅱ(IGF-Ⅱ)可促进多种细胞增殖,抑制细胞凋亡,其表达受基因印迹调控,IGF-Ⅱ基因印迹丢失(LOI)与多种肿瘤的发生相关。目前较少见IGF-Ⅱ与结直肠腺瘤关系的研究报道。目的:分析结直肠腺瘤中IGF-Ⅱ的表达及其基因印迹状态,初步探讨两者在结直肠腺瘤发生、发展中的作用。方法 :以免疫组化方法检测14例正常结直肠黏膜、12例增生性息肉和53例结直肠腺瘤组织中IGF-Ⅱ的表达,以聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法分析IGF-Ⅱ基因印迹状态。结果:IGF-Ⅱ的表达主要定位于细胞质,其表达在正常结直肠黏膜、增生性息肉和腺瘤组织中逐级递增(P<0.05)。正常黏膜、增生性息肉和腺瘤组织的IGF-Ⅱ杂合子基因型比例分别为42.9%、41.7%和60.4%。杂合子标本中,腺瘤组织的IGF-ⅡLOI发生率显著高于正常黏膜和增生性息肉(68.8%对16.7%和20.0%,P<0.05)。结论:IGF-ⅡLOI可能是导致IGF-Ⅱ蛋白表达增加,促进结直肠腺瘤发生以及向腺癌演变的重要机制。

【Abstract】 Background: Insulin-like growth factor Ⅱ(IGF-Ⅱ) promotes cell proliferation and inhibits cell apoptosis. The expression of IGF-Ⅱ is controlled by gene imprinting, and loss of imprinting(LOI) of IGF-Ⅱ has been found in some types of cancer. At present, there are few studies on the relationship between IGF-Ⅱ and colorectal adenoma. Aims: To appraise the expression of IGF-Ⅱ and the imprinting status of IGF-Ⅱ gene in colorectal adenoma, and to explore their effects on the development and progression of colorectal adenoma. Methods: Immunohistochemistry was used to determine the expression of IGF-Ⅱ in 14 normal colorectal mucosal tissues, 12 hyperplastic polyps and 53 colorectal adenomas. The imprinting status of IGF-Ⅱ was detected by polymerase chain reaction(PCR)-restriction fragment length polymorphism(RFLP) analysis. Results: IGF-Ⅱ expression was localized predominantly in the cytoplasm, which increased gradually from normal colorectal mucosa, hyperplastic polyp to adenomatous tissues(P <0.05). The positivity rate of IGF-Ⅱ DNA heterozygote was 60.4% in colorectal adenoma, 41.7% and 42.9% in hyperplastic polyps and normal mucosal tissues, respectively. In specimens of IGF-Ⅱ DNA heterozygote, the positivity rate of LOI of IGF-Ⅱ was significantly higher in colorectal adenoma than that in normal mucosal tissues and hyperplastic polyps(68.8% vs. 16.7%and 20.0%, P<0.05). Conclusions: LOI of IGF-Ⅱ may cause the increase of IGF-Ⅱ expression, thereby promotes the development of colorectal adenoma and the progression to adenocarcinoma.

  • 【文献出处】 胃肠病学 ,Chinese Journal of Gastroenterology , 编辑部邮箱 ,2009年03期
  • 【分类号】R735.34
  • 【下载频次】13
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